Is there testing available for Duffy null neutropenia?

Testing for Duffy-Null Neutropenia

Genetic testing for the Duffy-null genotype (mutation in ACKR1/DARC gene) is available and recommended to confirm the diagnosis of benign ethnic neutropenia in patients with unexplained low neutrophil counts. 1

Understanding Duffy-Null Neutropenia

Duffy-null neutropenia, also known as benign ethnic neutropenia (BEN), is characterized by:

• Lower absolute neutrophil count (ANC) values without increased risk of infection
• Associated with a mutation in the ACKR1/DARC gene
• Common in individuals of African (approximately two-thirds of Black patients in the US), Middle Eastern, and West Indian descent 1
• Reference range for neutrophils in individuals with Duffy-null status is approximately 1210-5390 cells/μL 1

Diagnostic Testing Options

Genetic Testing

• Direct testing for the Duffy-null genotype (mutation in ACKR1/DARC gene) is available and is the most definitive method to confirm the diagnosis 1
• This typically involves testing for the rs2814778-CC variant, which is the genetic marker for Duffy-null status 2

Clinical Context for Testing

• Testing is particularly important in:
  • Patients with unexplained neutropenia without increased infection risk
  • Patients from populations with high prevalence of the trait (African, Middle Eastern, West Indian descent)
  • Patients receiving medications where inappropriate dose reductions might occur due to perceived neutropenia (e.g., lenalidomide, pomalidomide) 3

Clinical Implications of Testing

• Confirming Duffy-null status prevents:

  • Unnecessary bone marrow biopsies
  • Inappropriate medication dose reductions
  • Exclusion from clinical trials
  • Misdiagnosis of neutropenia as pathological 2

• In cancer treatment, particularly multiple myeloma:

  • Patients with Duffy-null status should not have lenalidomide or pomalidomide doses reduced based solely on low ANC values 3, 1
  • Inappropriate dose reductions can lead to suboptimal treatment outcomes 1

Testing Availability and Implementation

• Genetic testing for Duffy-null status is becoming more widely available in clinical settings
• A study at a tertiary children's hospital found that Duffy-null neutropenia was present in 77.7% of leukopenia/neutropenia referrals, with particularly high prevalence in Yemeni (96.6%), African American (91%), and non-Middle Eastern (52.9%) patients 4
• Broader genetic screening for rs2814778 across all populations could provide more accurate understanding of white blood cell counts and mitigate resulting health disparities 2

Important Clinical Considerations

• Race alone is not an accurate predictor of Duffy-null status - genetic testing provides definitive diagnosis 2
• Neutrophil function is not impaired in individuals with Duffy-null trait - studies show no increased risk of infection 5
• G-CSF treatment is not routinely indicated for BEN alone 1
• Routine monitoring of neutrophil counts is unnecessary in asymptomatic individuals with established BEN 1

By confirming Duffy-null status through genetic testing, clinicians can avoid unnecessary interventions and ensure appropriate medication dosing, particularly in cancer treatment regimens where neutropenia might otherwise lead to suboptimal therapy.